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|Title||Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Wang, M, Menon, R, Mishra, S, Patel, AP, Chaffin, M, Tanneeru, D, Deshmukh, M, Mathew, O, Apte, S, Devanboo, CS, Sundaram, S, Lakshmipathy, P, Murugan, S, Sharma, KKumar, Rajendran, K, Santhosh, S, Thachathodiyl, R, Ahamed, H, Balegadde, AVijay, Alexander, T, Swaminathan, K, Gupta, R, Mullasari, AS, Sigamani, A, Kanchi, M, Peterson, AS, Butterworth, AS, Danesh, J, Di Angelantonio, E, Naheed, A, Inouye, M, Chowdhury, R, Vedam, RL, Kathiresan, S, Gupta, R, Khera, AV|
|Journal||J Am Coll Cardiol|
|Date Published||2020 08 11|
|Keywords||Adult, Aged, Bangladesh, Case-Control Studies, Coronary Artery Disease, Female, Genome-Wide Association Study, Humans, India, Male, Middle Aged, Multifactorial Inheritance|
BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.
OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPS for South Asians.
METHODS: This GPS was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPS reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPS reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.
RESULTS: The GPS, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p
CONCLUSIONS: The new GPS has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.
|Alternate Journal||J Am Coll Cardiol|
|PubMed Central ID||PMC7592606|
|Grant List||UM1 HG008895 / HG / NHGRI NIH HHS / United States |
MC_QA137853 / MR / Medical Research Council / United Kingdom
T32 HL007208 / HL / NHLBI NIH HHS / United States
MC_PC_17228 / MR / Medical Research Council / United Kingdom
K08 HG010155 / HG / NHGRI NIH HHS / United States